Nitro group photoreduction of 4-(2-nitrophenyl)- and 4-(3-nitrophenyl)-1,4- dihydropyridines

Article abstract of DOI:10.1016/j.chemphys.2010.06.007

The photoprocesses of nifedipine, a 4-(2-nitrophenyl)-1,4-dihydropyridine, and nimodipine and nitrendipine, two 3-nitrophenyl Hantzsch-type analogues, were studied by steady-state and time-resolved methods. The intramolecular photoreduction of nifedipine

Full text of DOI:10.1016/j.chemphys.2010.06.007

Chemical Physics 373 (2010) 153–158
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Nitro group photoreduction of 4-(2-nitrophenyl)- and
4-(3-nitrophenyl)-1,4-dihydropyridines
*
Helmut Görner
Max-Planck-Institut für Bioanorganische Chemie, D-45413 Mülheim an der Ruhr, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The photoprocesses of nifedipine, a 4-(2-nitrophenyl)-1,4-dihydropyridine, and nimodipine and nitrendi-
pine, two 3-nitrophenyl Hantzsch-type analogues, were studied by steady-state and time-resolved meth-
ods. The intramolecular photoreduction of nifedipine into its nitrosophenyl product takes place within a
few ns. The quantum yield of conversion is Ured = 0.3 and does not depend significantly on the oxygen
concentration and solvent properties. Formation of the fully reduced 4-(2-aminophenyl)-1,4-dihydropyr-
idine as minor product is indicated by fluorescence spectroscopy. The photoreduction of nimodipine and
nitrendipine is inefficient, Ured = 0.002 in acetonitrile, but markedly enhanced in the presence of donors
such as triethylamine (TEA) and 2-propanol, e.g. for TEA Ured is up to 0.03. The triplet states of nimodi-
pine and nitrendipine were characterized. They react intermolecularly with TEA and 2-propanol, forming
radicals as intermediates and eventually several reduction products.
Received 7 April 2010
In final form 2 June 2010
Available online 8 June 2010
Keyword:
Intramolecular intermolecular
photoreduction triplet
Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction
1,4-dihydropyridines not containing a nitro group [28,29]. The 3-
nitrophenyl analogues of nifedipine are of interest since intramo-
Nifedipine is a calcium channel blocker and frequently used in
the treatment of hypertension or cardiovascular diseases [1–3]. It
is sensitive to UV radiation and the photochemistry is therefore
the subject of various studies [1–18]. The major photoproduct is
lecular H-atom transfer is likewise not possible [24]. Examples
are nimodipine and nitrendipine, see Chart 1. Apparently, a 4-(3-
nitrophenyl) group has only a small effect on the photochemical
reactions of 1,4-dihydropyridines. However, evidence has been
found for intermolecular H-transfer from methanol and electron
transfer from triethylamine (TEA) in the photochemistry of some
4-(3-nitrophenyl)-1,4-dihydropyridines [24]. The reactivity of
nifedipine toward singlet molecular oxygen is moderate and the
UD values are 0.02–0.04 [14]. The photoproducts of nimodipine
and nitrendipine obtained in the presence of TEA contain either a
nitroso, a hydroxylamino or an amino group resulting from reduc-
tion of the nitro group, whereas the dihydropyridine moiety is con-
served intact [24]. The nitroso, hydroxylamino and amino-product
forms of irradiated nicardipine, a 4-(3-nitrophenyl)-1,4-dihydro-
pyridine, in methanol have been identified [28]. The photoinduced
aromatization has been achieved for a series of unsymmetrically
substituted 1,4-dihydropyridines and the resulting products were
identified [26]. The photoreduction should be enhanced in the
presence of an alcohol, such as 2-propanol.
Here the photochemical reactions of nifedipine, nimodipine and
nitrendipine were studied by steady-state and time-resolved tech-
niques. The conversion of nifedipine to the corresponding 4-(2-
nitroso)pyridine ONPhPy1 does not involve an observable triplet
state and ONPhPy1 was found to be stable. A light-induced fluores-
cence increase due to formation of 4-(2-aminophenyl)-1,4-dihy-
dropyridine as product in trace amounts has not been reported
as yet. The results were compared with those of the 4-(3-nitro-
2,6-dimethyl-4-(2-nitrosophenyl)-3,5-pyridinedicarboxylic
acid
dimethyl ester (ONPhPy1), the corresponding 4-(2-nitroso)pyri-
dine, Scheme 1. The photoconversion has been monitored in the
UV range [1–8] and is accompanied by the formation of an absorp-
tion band centered at 770 nm due to the nitrosophenyl entity of
ONPhPy1 [9–11]. A similar photoreduction to a nitrosophenyl com-
pound has been reported for furnidipine [19].
The proposed key-step of the photoconversion to ONPhPy1 is an
intramolecular electron transfer from the dihydropyridine moiety
to the nitro group [15]. Evidence has been found for formation of
a zwitterionic intermediate in the photochemistry of 4-(2-nitro-
phenyl)-1,4-dihydropyridines at ꢀ196 °C [15]. Alternatively, a
biradical prior to water elimination can be considered [15]. The
putative triplet biradical has been observed by EPR spectroscopy
in the photolysis of nifedipine at ꢀ196 °C [10]. For nifedipine the
quantum yield of formation of singlet oxygen (UD), which is re-
lated to the quantum yield of intersystem crossing (Uisc), is close
to zero [14].
Several studies deal with the photochemistry of 4-(3-nitro-
phenyl)-1,4-dihydropyridines [20–27]; a few others are related to
* Tel.: +49 2083063593; fax: +49 2083063951.
E-mail address: goerner@mpi-muelheim.mpg.de
0301-0104/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.chemphys.2010.06.007

154
H. Görner / Chemical Physics 373 (2010) 153–158
H3C
HN
CO2CH3
H
H3C
CO2CH3
hν
H2O
N
-
ON
O2N
H3C
CO2CH3
H3C
CO2CH3 (nifedipine)
(ONPhPy1)
Scheme 1.
H3C
CH3
O
O
O
CH3
O
NO2
NO2
H3C
H3C
HN
O
HN
nitrendipine
nimodipine
CH3
H
H
O
H3C
O
H3C
O
O
CH3
Chart 1.
phenyl)-1,4-dihydropyridines, where Uisc is above zero. These pho-
toreactions occur intermolecularly and involve H-atom or electron
transfer from an added donor to the triplet state. The triplet states
of nimodipine and nitrendipine in acetonitrile were characterized.
In the presence of TEA a secondary transient intermediate was ob-
served which is ascribed to a radical.
3. Results
3.1. Photoprocesses of nifedipine
The absorption spectrum of nifedipine in acetonitrile has a ma-
jor peak at 250 nm and a broad band centered at 360 nm. A photo-
product with maximum at kp = 280 nm and a peak at 312 nm and
two isosbestic points at k1 = 255 and k2 = 327 nm appear upon
pulsed excitation at 308 nm (Fig. 1, inset). The absorption changes
as a function of the incident energy in Fig. 1 show that the absence
or presence of oxygen has no effect. The spectral changes are the
same upon continuous irradiation at 313 nm. An example for such
a photoconversion of nifedipine in aqueous solution is shown in
Fig. 2. Similar results were found in a series of solvents, some char-
acteristic data are compiled in Table 1.
The major photoproduct of nifedipine is the corresponding 4-
(2-nitrosophenyl)pyridine, ONPhPy1, Scheme 1 [1–15]. The quan-
tum yield Ured of conversion is insensitive to the presence or ab-
sence of oxygen. This is in agreement with the recent literature
[15]. For nifedipine in acetonitrile it was found that variation of
kirr = 254 or 366 nm has no effect on Ured. Moreover, Ured depends
only little on solvent properties, the values obtained using illumi-
nation at 308/313 nm are listed in Table 2. Ured is between 0.2 and
0.3.
2. Experimental
Nifedipine, nimodipine (2-methoxyethyl-1-methylethyl-2,6-di-
methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate)
and nitrendipine (ethylmethyl-2,6-dimethyl-4-(3-nitrophenyl)-
1,4-dihydropyridine-3,5-dicarboxylate) were from Sigma, the
other compounds (Aldrich) and the solvents (Merck) were used
as received (acetonitrile: Uvasol) or purified by distillation: TEA.
The molar absorption coefficient at 350 nm of nifedipine is
e
350 = 7 ꢁ 103 Mꢀ1cmꢀ1 [16]. The absorption spectra were moni-
tored on a UV/vis spectrophotometer (HP, 8453). The emission
and excitation spectra were measured using a spectrofluorimeter
(Eclypse, Cary). For photoconversion at 313 nm, Hg lamps and
either a band-pass filter or a monochromator were used. The
photoconversion was carried out after bubbling argon (or oxygen)
through the solutions prior to and during irradiation. To compare
UV and near infrared spectral regions the samples were analyzed
in 0.1 and 10 mm cells or else the solutions were 100 times diluted.
Analysis was partly carried out by HPLC, however, without com-
parison with authentic products. A reverse phase column (ODS-
2
Aobs
3HD, PerfectSilTarget, 3 l
m, 0.8 ml minꢀ1) was used with mobile
phase gradient, composed of 0.5% trifluoroacetic acid and either a
1:5 mixture of acetonitrile and water or neat acetonitrile as eluent.
The quantum yield of reduction (Ured) was determined using the
aberchrome 540 actinometer [30]. An excimer laser (Lambda Phys-
ik, EMG 200, pulse width of 20 ns and energy <100 mJ) was used
for excitation at 308 nm. The absorption signals were measured
with two digitizers (Tektronix 7912AD and 390AD). Relative yields
were obtained using optically matched solutions (A308 = 1.5–2.0).
Photoreduction of the substrate was also achieved upon repetitive
pulsing at 308 nm. Note that nifedipine is thermally degrading in
water at pH 8. Therefore, photoreduction was not carried out in
aqueous solution, except for one case, where the overall irradiation
time was short compared to the time required for thermal degra-
dation. The measurements refer to 24 2 °C and, unless otherwise
indicated, to deoxygenated solution.
1.0
1
0.5
0
250
300
350
λ (nm)
400
0
0
100
No of pulses
Fig. 1. Plots of A280 (open) and A380 (full) for nifedipine (0.1 mM) in argon-(circles)
and oxygen-saturated (triangles) acetonitrile as a function of 308 nm excitation;
inset: absorption spectra at 0, 20 and 100 pulses.

H. Görner / Chemical Physics 373 (2010) 153–158
155
Irradiation of nifedipine in high concentration, e.g. 8–30 mM, in
argon-saturated acetonitrile was carried out to follow the appear-
ance of an absorption band centered at 770 nm (Fig. 3, inset). The
molar absorption coefficient of ONPhPy1 was found to be
1.5
Aobs
e
770 = 60 Mꢀ1 cmꢀ1, in agreement with values in the literature
1.0
0.5
0
[9–11]. An example of the absorption changes as a function of time
is shown in Fig. 3. Product analyses, carried out by HPLC, reveal one
major product: ONPhPy1, which is not further affected upon pro-
longed illumination. Interestingly, ONPhPy1 in acetonitrile was
found to be stable for several days. No transient was detected upon
photolysis of nifedipine in argon-saturated acetonitrile. The absor-
bance at 300–380 nm decreases during the pulse. This bleaching
remains permanent (Fig. 4) and indicates conversion without
involvement of a triplet state.
1
0
250
300
350
λ (nm)
400
0
100
Time (s)
3.2. Fluorescence of photoreduced nifedipine
Fig. 2. Plots of A260 (o) and A360 (N) for nifedipine in argon-saturated acetonitrile–
water (1:9, pH 8) as a function of time of irradiation at 313 nm; inset: absorption
spectra, 10 s interval.
The fluorescence spectrum of nifedipine in acetonitrile has no
marked peak and is very weak. After irradiation at 308 or
313 nm a new photoinduced fluorescence emission with peak cen-
tered at 440 nm appears which becomes stronger upon further
illumination. A plot of the intensity If as a function of the time of
irradiation at 313 nm is shown in Fig. 5. It is noteworthy that the
fluorescence excitation maximum at 370 nm is red-shifted by
60 nm with respect to that of the absorption at kp = 312 nm. The
suggested reason is strong fluorescence of a trace product rather
than of ONPhPy1 itself. A comparison with absorption changes ex-
cludes secondary photolysis as origin of the fluorescence. Further-
more, the emission and excitation spectra (inset (a) of Fig. 5) are
attributed to 4-(2-aminophenyl)-1,4-dihydropyridine, the fully re-
duced product. However, the 4-(2-hydroxylaminophenyl)-1,4-
dihydropyridine (the precursor) is expected to have similar
spectra.
Table 1
Absorption maximum of nitrophenyl-1,4-dihydrophenylpyridines upon irradiation
and isosbestic pointsa.
Compound
Nifedipine
Solvent
k1 (nm)
kp (nm)
k2 (nm)
Benzene
<290
330
327
325
328
320
320
Acetonitrile
2-Propanol
H2Ob
2-Propanol
2-Propanol
255
260
260
265
265
280, 310sh
280, 310sh
280, 310
290
Nimodipine
Nitrendipine
285
a
Using kirr = 313 nm.
No thermal effect within a short time interval of <5 min.
b
In fact, thermal reduction of ONPhPy1 in argon-saturated aceto-
nitrile (plus H+/Zn) leads to a red-shifted absorption band centered
at 380 nm and a similar fluorescence excitation spectrum and an
emission band at 440 nm (inset (b) of Fig. 5). This is in agreement
with a literature report [31]. Note that such a thermal reduction
takes place only after vigorous deoxygenation. The 440 nm band
obtained in the dark is similar (but not the same) as the photoin-
duced spectrum.
Table 2
a
Quantum yield of conversion of nifedipine to ONPhPy1
.
b
Solvent
Ured
Ured
Benzene
0.25
0.30
0.33
0.30
0.32
0.32
0.22
0.26
0.3
Acetonitrile
Methanol
2-Propanol
H2Oc pH 7
H2Oc pH 11
0.3
0.3
a
b
c
In argon-saturated solution using irradiation at 313 nm.
Using pulses at 308 nm.
Plus 1% methanol, pH 7.
3.3. Photoreduction of 3-nitrophenyldihydropyridines
The 360 nm band of the absorption spectrum of nimodipine in
argon-saturated propanol decreases upon irradiation at 313 nm
(Fig. 6) and the spectral changes (inset of Fig. 6) are analogous to
those of nifedipine. For nimodipine or nitrendipine in argon-satu-
rated propanol Ured = 0.02, while it is only 0.001 in acetonitrile (Ta-
ble 3). The changes are similar in argon-saturated acetonitrile in
1.0
0.8
0.4
1
5
A
Aobs
4
2
3
0
0.5
400
600
800
λ (nm)
0
0
2000
Time (s)
Fig. 3. Plots of A380 (d, 0.1 mm) and A760 (D, 1 cm) of the conversion of nifedipine
Fig. 4. Transient absorption spectra of nifedipine in argon-saturated acetonitrile at
(12 mM) to ONPhPy1 in air-saturated acetonitrile as a function of time of irradiation
at 313 nm; inset: absorption spectra at 400, 2000 and 4000 s, 3–5, respectively.
20 ns (s), 1
300 (upper) and 370 nm (lower).
ls (D), 10 ls (h) and 1 ms (N) after the 308 nm pulse; insets: kinetics at

156
H. Görner / Chemical Physics 373 (2010) 153–158
1.0
1.0
2
2
A
1
If
a
Aobs
Aobs
0.5
a
b
If
If
0
300
350
λ (nm)
λ (nm)
450
350
400
0.5
1.0
1
1.0
If
I f
0.5
0.5
b
0
350
400
λ (nm)
450
500
350
400
450 λ (nm)
0
0
100
Time (s)
0
200
Time (s)
0
50
Fig. 7. Plots of A290 (d) and the fluorescence intensity at 460 nm (D, kexc = 350 nm)
Fig. 5. Plots of A260 (o) and A380 (d) and the relative fluorescence intensity at
440 nm ( , kexc = 350 nm) of nifedipine in acetonitrile as a function of time of
irradiation at 313 nm; insets: emission and excitation spectra (a) after 1 min
irradiation and (b) thermally; argon-saturated, in the presence of 1 M HClO4 3 (full)
and 10 min (broken) after addition of Zn powder.
for nitrendipine in argon-saturated acetonitrile in the presence of 0.1 M TEA as a
function of the time of irradiation at 313 nm; inset: (a) absorption spectra at 0, 30,
80, 120 and 180 s and (b) fluorescence emission and excitation spectra after 3 min
irradiation.
D
1.0
2
Aobs
Conv.
A
1
0.5
0
250
300
λ (nm)
350
400
0
Fig. 8. Transient absorption spectra of (a) nimodipine and (b) nitrendipine in
argon-saturated acetonitrile at 20 ns (s) and 1 ls (D) after the 308 nm pulse;
0
300
Time (s)
insets: kinetics at 460 nm.
Fig. 6. Plots of A260 (o) and A360 (N) and the fraction of decomposition for
nimodipine (d) in argon-saturated 2-propanol as function of the time of
a
irradiation at 313 nm; inset: absorption spectra at 0 and 500 s.
in argon-saturated acetonitrile is ca. 0.3 ls. The triplet state is
quenched by oxygen and 2-propanol. In the presence of 2-propanol
a longer lived radical is formed. Decay of the triplet state is also
accelerated on addition of TEA, thereby yielding a radical anion
which decays within 0.005–0.5 ms (not shown).
Table 3
Quantum yield of reduction of 4-(3-nitrophenyl)-1,4-dihydrophenylpyridinesa.
Compound
Nimodipine
Solvent
Additive
Ured
Acetonitrile
Acetonitrile
Methanol
None
0.002
0.01
0.02
0.03
TEAb
4. Discussion
Methanol
2-Propanol
2-Propanol
4.1. Mechanism of photoreduction of nifedipine
Nitrendipine
Acetonitrile
Acetonitrile
2-Propanol
None
0.002
0.03
0.02
TEAc
2-Propanol
The absorbance of nifedipine at 300–380 nm decreases during
the pulse and this bleaching remains permanent (Figs. 1–4), indi-
cating conversion without involvement of a triplet state. This is
in agreement with a negligible UD value [14]. The fast conversion
of nifedipine into ONPhPy1 without involvement of a triplet state is
compatible with intramolecular H-atom transfer and a biradical
intermediate [15], Scheme 2, Ured = 0.3. The reaction could take
place in the excited singlet state, but the triplet pathway in most
nitroarenes [32–34] makes this singlet pathway unlikely. The con-
version is relatively insensitive to variation of the solvent polarity
(Table 2).
a
b
c
In argon-saturated solution using kirr = 313 nm.
0.1 M.
0.7 M.
the presence of TEA, an example is shown in Fig. 7 for nitrendipine.
Insets (a) of the absorption spectra prior to and upon irradiation at
313 nm and (b) of the fluorescence emission and excitation spectra
of the photoproducts are consistent with reduction via intermolec-
ular electron transfer.
The transient absorbance of nimodipine and nitrendipine in
acetonitrile upon 308 nm excitation is weak, examples are shown
in Fig. 8. The end-of-pulse transient is attributed to the triplet
state. The lifetime of the nimodipine or nitrendipine triplet state
A minor photoproduct of nifedipine could be the corresponding
nitrophenylpyridine. This photodehydrogenation has been pro-
posed to be enhanced by UV-light [2], but this idea was later re-
jected [3]. Apparently, the photoreduction stops at the stage of

H. Görner / Chemical Physics 373 (2010) 153–158
157
H3C
HN
R
H3C
HN
H3C
N
R
R
-H+
-OH-
H
hν
+
•
nifedipine
•
ONPhPy
1
-
•
•
-
NO2H
H3C
R'
H3C
H3C
R'
R'
NO2
NO2H
Scheme 2.
4.3. Comparison with photoreduction of other nitroarenes
H3C
HN
R
H3C
HN
R
hν
+DH2
H
H
The full intramolecular reduction of nifedipine into the 4-(2-
aminophenyl)-1,4-dihydropyridine, which requires six electron
equivalents, is feasible as minor side reaction (see above). A related
intermolecular full reduction into the corresponding 4-(3-amino-
phenyl)-1,4-dihydropyridines was not observed. For various nitro-
compounds the full reduction does not take place. For
nitrobenzene, a combination (self-termination) of the radicals
leads to dimerization products [32–34,37–44]. Apparently, this
radical dimerization is much more efficient than a pathway to
the amino-product. This is different for 1-nitro-9,10-anthraqui-
none and the 2-methyl derivative [45,46]. The first step is popula-
tion of the triplet state, then H-transfer from the alcohol generates
nitroAQ-derived radicals which combine bimolecularly into nitro-
AQ and nitrosoAQ. The same radical can be produced by electron
transfer from an amine. Further electron transfer steps occur,
whereby 1-aminohydroxylAQ is formed. The quantum yield of
complete reduction is up to 0.2. Various sensitizer-donor couples
with ketones and alcohols or amines can be used to achieve effi-
cient conversion. For 1-nitroAQs the carbonyl groups function as
H-atom acceptor sites [47].
-D
NO
NO2
-H2O
H3C
R'
H3C
R'
Scheme 3.
the nitroso compound. This is due to the absence of H-atom do-
nors. Nevertheless, further reduction of ONPhPy1 in 4-(2-hydroxyl-
aminophenyl)-1,4-dihydropyridine or 4-(2-aminophenyl)-1,4-
dihydropyridine, which requires the respective two or four addi-
tional electron equivalents, is indicated by fluorescence spectros-
copy, see Fig. 5. Oxidation of various 3,4-dihydropyimidin-2-
(1H)-ones and 1,4-dihydropyridines have been reported [35,36].
4.2. Photoreduction of 4-(3-nitrophenyl)-1,4-dihydropyridines
The quantum yield of formation of singlet molecular oxygen
using kirr = 355 nm is UD = 0.04, 0.02 and 0.001 for nitrendipine
in benzene, acetonitrile and ethanol, respectively [14]. This indi-
cates a low Uisc for 4-(3-nitrophenyl)-1,4-dihydropyridines and is
in agreement with a weak triplet state formation of nimodipine
(Fig. 8(a)) and nitrendipine (Fig. 8(b)) and a low Ured in acetonitrile.
In fact, Ured = 0.004 for nimodipine in acetonitrile, while
Ured = 0.01 in methanol [24]. A 10-fold enhancement in ethanol
5. Conclusion
The conditions for the efficient photoconversion of nifedipine
into its corresponding 4-(2-nitrosophenyl)pyridine were exam-
ined, the nature of the solvent has only a minor influence. The pho-
toreduction of nifedipine is a rare case, where the formation of a
stable nitroso compound is documented. The fully reduced 4-(2-
aminophenyl)-1,4-dihydropyridine as minor primary photoprod-
uct was observed by fluorescence spectroscopy. The triplet states
of nimodipine and nitrendipine in acetonitrile has been observed
by flash photolysis. The intermolecular photoreduction steps of
the two 3-nitrophenyl-1,4-dihydrophenylpyridines in the presence
of TEA and 2-propanol were analyzed.
(
Ured = 0.02, kirr = 366 nm) vs. acetonitrile (Ured = 0.002) has been
reported [25]. An enhancement of Ured was also found with TEA
[24]. Reactions of the triplet state of nimodipine and nitrendipine
with alcohols and TEA are indicated by weak longer lived tran-
sients at 400–500 nm (not shown). The photoprocess is ascribed
to electron transfer from TEA to the triplet state [2] and H-transfer
from the alcohol as reactive steps. HPLC analyses for nimodipine
and nitrendipine revealed more than three product peaks and
one of the primary photoproducts is nitrosoPhH2Py (Scheme 3), de-
rived via radical termination, step 3.
Acknowledgments
1ꢂO2NPhH2Py ! 3ꢂO2NPhH2Py ! O2NPhH2Py
ð1Þ
ð2Þ
ð3Þ
The author thanks Professor Wolfgang Lubitz for his support,
Mr. Henry Gruen for stimulating discussions and Mrs. Gabriele
Schmitz, Mr. Leslie-James Currell and Horst Selbach for technical
assistance.
3ꢂO2NPhH2Py þ NEt3 þ Hþ ! ꢀHO2NPhH2Py þ þꢀNEt3
2 ꢁ ꢀHO2NPhH2Py ! ONPhH2Py þ O2NPhH2Py þ H2O
No equilibrium between the HO2NPhH2Py and ꢀꢀO2NPhH2Py radi-
cals appears to be established in benzene or wet acetonitrile. The
TEA-derived radicals decay within 0.1 ms. The rather long ranging
intermediacy of the radicals excludes electron back transfer as a
major reaction which, however, occurs in the presence of DABCO.
A 3-hydroxylamino or 3-amino product is indicated by fluorescence
analysis of a 4-(3-nitrophenyl)-1,4-dihydropyridine/TEA system
(inset (b) of Fig. 7). For a series of unsymmetrically substituted
1,4-dihydropyridines reduction products have been characterized
[27]. Thermal degradation has also been reported for nitrendipine,
the rate is largest at pH 12 [21].
ꢀ
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